ACP-196 (Acalabrutinib) in Combination With Pembrolizumab, for Treatment of Hematologic Malignancies
KEYNOTE145
A Phase 1b/2 Proof-of-Concept Study of the Combination of ACP-196 (Acalabrutinib) and Pembrolizumab in Subjects With Hematologic Malignancies
1 other identifier
interventional
161
1 country
19
Brief Summary
This study is evaluating the safety, pharmacodynamics (PD), and efficacy of acalabrutinib and pembrolizumab in hematologic malignancies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2015
Longer than P75 for phase_1
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 7, 2015
CompletedFirst Posted
Study publicly available on registry
February 12, 2015
CompletedStudy Start
First participant enrolled
February 20, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 14, 2020
CompletedResults Posted
Study results publicly available
May 6, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
October 27, 2025
CompletedDecember 11, 2025
November 1, 2025
5.4 years
February 7, 2015
July 5, 2021
November 25, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (16)
Number of Participants With Treatment Emergent Adverse Events (AEs)
Treatment-emergent AEs were defined as those events that occurred on or after the first dose of study drug, through the treatment phase, and within 30 days following the last dose of study drug.
104 weeks
Number of Participants With Grade 3-4 Adverse Events
Severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03
104 weeks
Number of Participants With Grade 5 Adverse Events
Number of participants with CTCAE Grade 5 (fatal) adverse events
104 weeks
Number of Participants With Any Study-Drug Related AE
Study drug-related AEs were those assessed by investigator as related to study treatment.
104 weeks
Number of Participants With Grade 3-4 Study-Drug Related AE
The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher. Drug-related AEs were those assessed by investigator as related to study treatment.
104 weeks
Number of Participants With Grade 5 Study-Drug Related AE
Grade 5 (fatal) AEs assessed by investigator as related to study treatment.
104 weeks
Number of Participants With Any SAE
Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.
104 weeks
Number of Participants With Grade 3-4 Any SAE
Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher.
104 weeks
Number of Participants With Grade 5 Any SAE
Grade 5 events were fatal events. Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.
104 weeks
Number of Participants With Any Study Drug-Related SAE
Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. Drug-related AEs were those assessed by investigator as related to study treatment.
104 weeks
Number of Participants With Any Grade 3-4 Study Drug-Related SAE
Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher. Drug-related AEs were those assessed by investigator as related to study treatment.
104 weeks
Number of Participants With Any Grade 5 Study Drug-Related SAE
Grade 5 AEs were fatal events. Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. Drug-related AEs were those assessed by investigator as related to study treatment.
104 weeks
Number of Participants With AE Leading to Study Drug Discontinuation, Modification or Delay
AEs that discontinuation of study treatment, or a reduction in dosage, or a delay (temporary withholding) in treatment.
104 weeks
Number of Participants With AE Leading to Study Drug Discontinuation
An adverse event that resulted in the permanent discontinuation of study treatment in the study.
104 weeks
Number of Participants With AE Leading to Study Drug Delay
An adverse event that caused a temporary withholding of study treatment.
104 weeks
Number of Participants With AE Leading to Study Drug Modification
An adverse event that resulted in a reduction in the dosage of study treatment for that participant.
104 weeks
Secondary Outcomes (5)
Overall Response Rate
104 weeks
Duration of Response
104 weeks
Progression-free Survival
104 weeks
Overall Survival
104 weeks
Time to Next Treatment
104 weeks
Study Arms (1)
Acalabrutinib plus Pembrolizumab
EXPERIMENTALA nonrandomized study that will be conducted in 2 stages. In the first stage, (Safety), subjects will receive Acalabrutinib Dose A orally administered (PO) twice daily (BID) in combination with Pembrolizumab Dose B administered every 3 weeks (Q3W). The second stage was an expansion of Cohorts with the same dose regimen as the first stage. An additional expansion in subjects with Myelofibrosis was planned but not conducted.
Interventions
Intravenous Administered (IV)
Eligibility Criteria
You may qualify if:
- Diagnosis of a hematologic malignancy as documented by medical records and with histology based on criteria established by the World Health Organization (WHO).
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
- Agreement to use contraception during the study and for 90 days after the last dose of ACP-196 or 120 days after the last dose of pembrolizumab, if sexually active and able to bear or beget children.
- Completion of all therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥ 4 weeks before the start of study therapy.
- ANC ≥ 0.5 x 10\^9/L or platelet count ≥ 50 x 10\^9/L unless due to disease involvement in the bone marrow.
You may not qualify if:
- A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of study drugs, or put the study outcomes at undue risk.
- Central nervous system (CNS) involvement by lymphoma/leukemia
- Any therapeutic antibody within 4 weeks of first dose of study drugs.
- Total bilirubin \> 1.5 x ULN; and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3.0 x ULN.
- Estimated creatinine clearance of \< 30 mL/min, calculated using the formula of Cockcroft and Gault (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Acerta Pharma BVlead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (19)
Research Site
Tucson, Arizona, 85704, United States
Research Site
Los Angeles, California, 90095, United States
Research Site
Denver, Colorado, 80218, United States
Research Site
Washington D.C., District of Columbia, 20007, United States
Research Site
Niles, Illinois, 60714, United States
Research Site
Boston, Massachusetts, 2215, United States
Research Site
Rochester, Minnesota, 55905-0001, United States
Research Site
Omaha, Nebraska, 68198-7680, United States
Research Site
Columbus, Ohio, 43210, United States
Research Site
Greenville, South Carolina, 29605, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Dallas, Texas, 75246, United States
Research Site
Houston, Texas, 77030, United States
Research Site
San Antonio, Texas, 78217, United States
Research Site
Tyler, Texas, 75702, United States
Research Site
Fairfax, Virginia, 22031, United States
Research Site
Roanoke, Virginia, 24014, United States
Research Site
Vancouver, Washington, 98684, United States
Research Site
Yakima, Washington, 98902, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- Acerta Pharma
Study Officials
- STUDY DIRECTOR
AstraZeneca Clinical Study Information Center
1-877-240-9479 - information.center@astrazeneca.com
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 7, 2015
First Posted
February 12, 2015
Study Start
February 20, 2015
Primary Completion
July 14, 2020
Study Completion
October 27, 2025
Last Updated
December 11, 2025
Results First Posted
May 6, 2022
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.